Briassouli Efrossini, Goukos Dimitris, Daikos George, Apostolou Kleovoulos, Routsi Christina, Nanas Serafim, Briassoulis George
First Department of Internal Medicine, Medical School, University of Athens, Laikon Hospital, Athens, Greece.
First Department of Critical Care, Medical School, University of Athens, Evangelismos Hospital, Athens, Greece.
Nutrition. 2014 Oct;30(10):1185-94. doi: 10.1016/j.nut.2014.01.018. Epub 2014 Feb 22.
L-Alanyl-glutamine (L-Ala-Gln) is a pharmaco-nutrient commonly used in nutrition regimens due to its immunomodulatory effects. In critically ill patients who are septic, L-Ala-Gln was associated with an increase in mortality. The aim of this study was to investigate whether L-Ala-Gln modulated heat shock protein (Hsp)-72, 90-α, T helper (Th)1, Th2, and Th17 cytokine expression in the peripheral blood mononuclear cells (PBMC) of patients with severe sepsis.
Time-dose effects of L-Ala-Gln were compared with those of L-glutamine (L-Gln) and lipopolysaccharide (LPS) and to healthy controls. PBMCs were incubated with 1 or 10 μg/mL LPS, 5 or 10 mM L-Gln, and 5 or 10 mM L-Ala-Gln for different periods of time (0; 4; 24 h) when culture supernatants were harvested.
In both groups, basal Hsp72 increased over time (P < 0.02); Hsp90-α levels declined in controls (P < 0.02) but remained increased in septic patients (P < 0.02), not exhibiting any significant time-response trend. Both Glns suppressed Hsp72 in septic and controls at 10 mM by 4 h (P < 0.045) and Hsp90-α in the control group by 24 h (P < 0.045). LPS did not induce Hsps in either group. L-Ala-Gln did not induce any of the Th1, Th2, and Th17 cytokines in either group.
High doses of L-Gln or L-Ala-Gln do not induce any of the Th1, Th2, and Th17 cytokines in either healthy or septic human PBMCs. High Gln doses suppress Hsp72 in septic and control PBMCs. Hsp90-α time-series expression declines, contrasting the increasing trend of Hsp72 in healthy controls. Hsp90-α sustains increased levels in septic supernatants, showing a characteristic longitudinal behavior needed further elucidation.
L-丙氨酰-谷氨酰胺（L-Ala-Gln）是一种因其免疫调节作用而常用于营养方案的药物营养素。在脓毒症重症患者中，L-Ala-Gln与死亡率增加相关。本研究的目的是调查L-Ala-Gln是否调节严重脓毒症患者外周血单个核细胞（PBMC）中热休克蛋白（Hsp）-72、90-α、辅助性T细胞（Th）1、Th2和Th17细胞因子的表达。
将L-Ala-Gln的时间-剂量效应与L-谷氨酰胺（L-Gln）和脂多糖（LPS）的效应进行比较，并与健康对照进行比较。当收获培养上清液时，将PBMC与1或10μg/mL LPS、5或10 mM L-Gln以及5或10 mM L-Ala-Gln孵育不同时间段（0；4；24小时）。
在两组中，基础Hsp72均随时间增加（P < 0.02）；对照组中Hsp90-α水平下降（P < 0.02），但脓毒症患者中仍升高（P < 0.02），未表现出任何显著的时间-反应趋势。两种谷氨酰胺在10 mM时于4小时抑制脓毒症组和对照组中的Hsp72（P < 0.045），并在24小时抑制对照组中的Hsp90-α（P < 0.045）。LPS在两组中均未诱导Hsps。L-Ala-Gln在两组中均未诱导任何Th1、Th2和Th17细胞因子。
高剂量的L-Gln或L-Ala-Gln在健康或脓毒症人类PBMC中均不诱导任何Th1、Th2和Th17细胞因子。高剂量谷氨酰胺抑制脓毒症组和对照组PBMC中的Hsp72。Hsp90-α的时间序列表达下降，与健康对照组中Hsp72的增加趋势形成对比。脓毒症上清液中Hsp90-α水平持续升高，显示出一种需要进一步阐明的特征性纵向行为。
